Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa

HIV Clinical Trial

— Flucocrypto  

Official title:

Prospective Pilot Study to Evaluate a Standardized Management of Cryptococcal Meningitis in Patients Infected With HIV in Sub-Saharan Africa Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Complemented by Repeat Lumbar Punctures

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01715922
• Other study ID #: ANRS 12257 Flucocrypto
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: October 19, 2012
• Last updated: July 11, 2016
• Start date: May 2012
• Est. completion date: September 2016

Study information

• Verified date: July 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Burundi: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association of:

1. Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy

2. lumbar punctures to control intracranial pressure

can decrease mortality rate below 35% at 10 weeks.

This is a non-randomized open label pilot study, with standardized management of cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients will be enrolled.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: September 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• > 18 years

• HIV Infection

• First episode of cryptococcal meningitis on basis CSF India ink and/or CSF cryptococcal antigen.

• Glasgow > 9 after lumbar punctures

• Absence of peripheral focal deficit in the limbs

• informed consent signed

Exclusion Criteria:

• Hemoglobin <7.5 g / dl;

• neutrophils count <500/mm3;

• Platelets count <50 000/mm3;

• transaminases > 5 times upper limit of normal;

• Troubles with severe mental alertness Glasgow <9 after the initial lumbar puncture;

• focal neurological deficit in the limbs;

• Pregnancy or lactation on going;

• Ongoing systemic antifungal treatment;

• History of cryptococcal meningitis;

• Ongoing rifampicin and ritonavir treatment;

• Subject participating in another study with a risk of mutual interference on the interpretation of results.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• HIV
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Fluconazole
Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
• Flucytosine
Flucytosine (100 mg/kg/j) for 2 weeks

Procedure:
• lumbar punctures
lumbar punctures to control intracranial pressure

Locations

Country	Name	City	State
Burundi	CHU Kamenge	Bujumbura
Burundi	Hôpital Prince Régent Charles	Bujumbura
Burundi	Hôpital général	Bururi
Burundi	Hôpital général	Kayanza
Burundi	Hôpital général	Muyinga
Côte D'Ivoire	Service de Maladies Infectieuses & Tropicales - Hôpital Triechville	Abidjan
Côte D'Ivoire	Service de Neurologie - Hôpital Cocody	Abidjan

Sponsors (8)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	CHU Kamenge, BURUNDI, Hôpital Cocody, Hôpital de Treichville, Hôpital Necker-Enfants Malades, Hospital Avicenne, Institut de Médecine et Epidémiologie Appliquée (IMEA), Institut Pasteur

Countries where clinical trial is conducted

Burundi,  Côte D'Ivoire, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality rate		10 weeks	Yes
Secondary	Mortality rate		14 days and 24 weeks	Yes
Secondary	Percentage of patients with negative cerebrospinal fluid (CSF) cultures		14 days and 10 weeks	No
Secondary	Number of relapses of cryptococcal throughout the monitoring period		up to 24 weeks	No
Secondary	Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period	The IRIS diagnosis criteria will be those given in: Bicanic T, et al. Immune Reconstitution Inflammatory Syndrome in HIV-associated cryptococcal meningitis: a prospective study, J Acquir Immune Defic Syndr 2009; 51:130-134.	up to 24 weeks	No
Secondary	Number and severity of adverse events		up to 24 weeks	Yes
Secondary	Cerebrospinal fluid pressure evolution		up to 24 weeks	No
Secondary	Percentage of patients with undetectable viral load		24 weeks	No
Secondary	CD4 count		24 weeks	No
Secondary	Concentration of flucytosine in cerebrospinal fluid		28 days or 10 weeks	No
Secondary	Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)	on urines, plasma, CSF and whole blood fingerstick	at study entry	No
Secondary	CSF total volume discharged		up to 24 weeks	No
Secondary	Number of lumbar punctures performed		up to 24 weeks	No
Secondary	Concentration of fluconazole in plasma		28 days or 10 weeks	No
Secondary	Concentration of fluconazole in cerebrospinal fluid		28 days or 10 weeks	No
Secondary	Concentration of flucytosine in plasma		28 days or 10 weeks	No
Secondary	MICs of fluconazole	MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse	28 days	No

External Links

•   Sponsor web page